Although the oral administration of insulin is recognized as the safest and most attractive, insulin oral bioavailability is usually reduced due to the susceptibility to acidic and enzymatic degradation in the gastrointestinal (GI) tract and intrinsic low intestinal permeability. Nanoencapsulation of insulin is, thus, foreseen as a promising approach to overcome most of these drawbacks. The effect of the GI environment on the aggregation of alginate/dextran sulfate-based nanometric-sized particles, uncoated or double-coated with chitosan and albumin, and its further influence on insulin release and permeability at the cellular level, was investigated in vitro. The swelling and aggregation behavior of NPs in gastric conditions was accompanied by the prevention of insulin release. In intestinal conditions, the fast dissolution of uncoated NPs was responsible for a wide size distribution and for a burst release of insulin, while the size stability provided by albumin/chitosan-coating led to sustained release. Chitosan/albumin-coated NPs were able to significantly increase the permeability of insulin across the cell-based engineered intestinal models, further enhanced by the presence of a mucus layer and M-like cells. The influence of these models on insulin permeability was compared to the curve that better adjusted to the mathematical kinetics of insulin release from these biopolymeric-NPs. Thus, a correlation between the size behavior of NPs upon passage in the GI tract and both insulin release profile and permeation across intestinal in vitro models was addressed. These results provide proof-of-concept evidence that the GI passage of NPs has a major influence on the oral absorption of macromolecules.

Alginate–dextran sulfate-based particles obtained by emulsification/internal gelation technology can be considered suitable carriers for oral insulin delivery. A rational study focused on the emulsification and particle recovery steps was developed in order to reduce particles to the nanosize range while keeping insulin bioactivity. There was a decrease in size when ultrasonication was used during emulsification, which was more pronounced when a cosurfactant was added. Ultrasonication add-on aft...more

Abstract An oral delivery system intended for treatment of colon cancer in HT29 cancerous cells was investigated by encapsulating hSET1 antisense and SN38 anticancer in nanoparticles based on cysteine trimethyl chitosan (cysTMC) and carboxymethyl dextran (CMD). Studies have shown hSET1 as the main type of histone methyltransferase (HMT) complex, is significantly overexpressed in malignant cells. In this study, hSET1 antisense was employed to inhibit gene expression. Additionally, SN38 was incorp...more

Background Particle size is thought to be a critical factor affecting the bioavailability of nanoparticles following oral exposure. Nearly all studies of nanoparticle bioavailability focus on characterization of the primary particle size of the material as supplied or as dosed, and not on agglomeration behavior within the gastrointestinal tract, which is presumably most relevant for absorption.

Background The lung epithelium constitutes the first barrier against invading pathogens and also a major surface potentially exposed to nanoparticles. In order to ensure and preserve lung epithelial barrier function, the alveolar compartment possesses local defence mechanisms that are able to control bacterial infection. For instance, alveolar macrophages are professional phagocytic cells that engulf bacteria and environmental contaminants (including nanoparticles) and secrete pro-inflammatory c...more

Glucagon like peptide-1 (GLP-1) is an incretin hormone that is in the pipeline for type 2 diabetes mellitus (T2DM) therapy. However, oral administration of GLP-1 is hindered by the harsh conditions of the gastrointestinal tract and poor bioavailability. In this study, three nanosystems composed by three different biomaterials (poly(lactide-co-glycolide) polymer (PLGA), Witepsol E85 lipid (solid lipid nanoparticles, SLN) and porous silicon (PSi) were developed and loaded with GLP-1 to study their...more

Abstract Porous silicon (PSi) based particulate systems are emerging as an important drug delivery system due to its advantageous properties such as biocompatibility, biodegradability and ability to tailor the particles' physicochemical properties. Here, annealed thermally hydrocarbonized PSi (AnnTHCPSi) and undecylenic acid modified AnnTHCPSi (AnnUnTHCPSi) microparticles were developed as a PSi-based platform for oral delivery of insulin. Chitosan (CS) was used to modify the AnnUnTHCPSi micropa...more

Chitosan nanoparticles (NC) have excellent capacity for protein entrapment, favorable epithelial permeability, and are regarded as promising nanocarriers for oral protein delivery. Herein, we designed and evaluated a class of core shell corona nanolipoparticles (CSC) to further improve the absorption through enhanced intestinal mucus penetration. CSC contains chitosan nanoparticles as a core component and pluronic F127-lipid vesicles as a shell with hydrophilic chain and polyethylene oxide PEO a...more

Abstract Caco-2 based cell models have been the gold standard in vitro method to study intestinal drug permeability, despite the absence of many important features with major influence in the drug absorption mechanism. In the present work, a triple co-culture comprising Caco-2, HT29-MTX and Raji B cells was established to mimic in a closely way the human intestinal epithelium, presenting the main components in the process of drug absorption, namely the absorptive cells that resemble enterocytes,...more

Abstract Alginate-dextran sulfate (ADS) microgel has been used to protect insulin from gastrointestinal attack and as a carrier to promote insulin permeation through intestinal epithelium. The throughput of ADS submicron particles generation by emulsification/internal gelation is limited by its wide size distribution. The aim of this work was to study the recovery protocol influence on ADS particles through the determination of its impact on particles’ size distribution and bioactivity. ADS part...more

Abstract We previously reported that insulin-entrapped chitosan complexed carboxymethylated iota-carrageenan (CS/CMCi) particles exhibit pH-responsive swelling behavior. However, the particles’ stability in the enzymatic gastrointestinal environment, their drug permeability mechanism, and related in vivo studies have not been discussed to date. In this study, we investigated the stability, muco-adhesiveness, transport mechanism and in vivo assessment of the particles. The particles retained thei...more

BACKGROUND: Subcutaneous injection of insulin can lead to problems such as hypoglycemia and edema. OBJECTIVE: The purpose of this research was to evaluate the effect of oral insulin-coated trimethyl chitosan nanoparticles on control of glycemic status, IGF-1 and IGF-2 levels, and apoptosis in the hippocampus of rats with diabetes mellitus. METHODS: Insulin-coated trimethyl chitosan nanoparticles were prepared by the polyelectrolyte complex method (PEC) method. Insulin loading content, loading ef...more

Abstract Recently, nanoemulsions have been employed for different applications including food and drug industries for efficient nutrient delivery system. In this study, vitamin D (a lipophilic molecule) was encapsulated in fish oil for higher oral bioavailability. The oil-in-water nanoemulsion was formulated by ultrasonication technique with a droplet size range of 300–450 nm and a shelf life of more than 90 days. The influence of oil, water and surfactant concentration was investigated by phase...more

Abstract We are introducing design, development and preliminary feasibility study of nanocomposites (made of Food and drug administration approved layered montmorillonite (Mt) and biodegradable polymer Poly lactic- co -glycolic acid (PLGA)), as a vehicle for oral administration of insulin. A systematic study on the variation of Mt-PLGA ratio was focused to reduce particles to the submicron size range while maintaining insulin's bioactivity. The synthesized Insulin-Mt-PLGA nanocomposites were suc...more